Little is known about the nature of circulating parathyroid hormone in metabolic diseases of bone or in clinical disturbances of parathyroid function. It is the purpose of this project to isolate parathyroid hormone, determine the structure of the polypeptide, elucidate the mechanism of action of the hormone, and to develop a clinically useful test for circulating parathyroid hormone. From these studies it is expected that one can understand the pathophysiology of certain metabolic diseases of bone and endocrine disturbances. The entire structure of bovine as well as porcine parathyroid hormone has been determined using the automated sequentor technique. A similar approach has allowed determination of the structure for the first 37 residues of human parathyroid hormone. Synthetic polypeptides representing the first 34 residues of bovine as well as human parathyroid hormone have been prepared. These molecules show all the biological properties of the native hormonal polypeptide. The highly sensitive specific radioimmunoassay for the hormone has been developed and is being modified further for potential use as a highly specific clinical tool. Recent studies show that the mechanism of action of purified hormone is mediated through direct hormonal activation of adenylate cyclase in bone and kidney.